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Introduction: Major burns and the intensive care required induce numerous physiologic changes and stress responses that impact recovery for months after hospital discharge. Little is known about sleep quantity and quality after index hospitalization discharge. We report on actigraphy and sleep outcome data from subjects enrolled in a prospective trial of home-based virtual rehabilitation (HBVR) after burn injury. Methods: We conducted a randomized controlled trial of a HBVR program over 12 weeks after index hospitalization. In both HBVR and control (usual care) groups, subjects were provided a wrist actigraphy accelerometer device (Garmin vívofit®) to wear. Sleep data were retrieved remotely and analyzed. Actigraphy data were defined a priori as complete if subjects had 5 out of 7 days of actigraphy wear in a week. Average weekly sleep was calculated and reported by group assignment. Sleep-relevant and fatigue outcomes were measured by PROMIS questionnaires at randomization (discharge + 0–30 days), 12-weeks, and 12-months. Descriptive statistics were used for comparisons and linear mixed effect model were used to evaluate trends in PROMIS T-scores between groups. Results: Fifty subjects were enrolled and 48 had complete sleep data. Mean age was 38 ± 14 years and mean burn size was 16 ± 13 % TBSA with a majority of subjects male (71 %). Average sleep duration was within general population norms, with little difference between subjects in the intervention and controls groups in the 12 weeks after study randomization (7.3 vs.7.2 h respectively, p = 0.25). Subjects in control group spent more time in light sleep (4.1 vs. 3.9 h, p

Determining the size of a burn injury is a critical metric in the care of the burn patient. Several long-standing methods exist to estimate burn size to include the Rule of Nines, Lund-Browder Chart, and Palmar method; all of which remain in clinical use today. Development and use of these metrics first began in the late 1800s. Understanding these clinical tools and others, with an appreciation of their development, limitations, and utility, is important for the competent burn care clinician today. This review provides an evolutional history for these metrics and use in clinical practice.

Abstract Skin broadly protects the human body from undesired factors such as ultraviolet radiation and abrasion and helps conserve body temperature and hydration. Skin’s elasticity and its level of anisotropy are key to its aesthetics and function. Currently, however, treatment success is often speculative and subjective, and is rarely based on skin’s elastic properties because there is no fast and accurate non-contact method for imaging of skin’s elasticity. Here we report on a non-contact and non-invasive method to image and characterize skin’s elastic anisotropy. It combines acoustic micro-tapping optical coherence elastography (AμT-OCE) with a nearly incompressible transversely isotropic (NITI) model to quantify skin’s elastic moduli. In addition, skin sites were imaged with polarization sensitive optical coherence tomography (PS-OCT) to help define fiber orientation. Forearm skin areas were investigated in five volunteers. Results clearly demonstrate elastic anisotropy of skin in all subjects. AμT-OCE has distinct advantages over competitive techniques because it provides objective, quantitative characterization of skin’s elasticity without contact, which opens the door for broad translation into clinical use. Finally, we demonstrate that a combination of multiple OCT modalities (structural OCT, OCT angiography, PS-OCT and AμT-OCE) may provide rich information about skin and can be used to characterize scar.

Abstract Background The survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long‐term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations. Methods The 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety‐four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log‐rank test was used to compare the difference in mortality between two populations and presented by the Kaplan–Meier curves. A multivariate Cox proportional hazards regression was used to determine the independent predictors of all‐cause mortality. Results The overall 30‐day, 1‐year, and 5‐year survival rates were 74%, 44.3%, and 16.6%, respectively, with a median survival of 10 months. There was no significant difference in survival rate between the two races (p‐value = 0.55). The 1‐year survival rate improved significantly during the study timeline in the AA population (13.3% during 1975–1998, 40.9% during 1999–2004, 50% during 2005–2010, and 59.7% during 2011–2016, p‐value = 0.0064). Age of diagnosis, type of tumor, disease stage, and chemotherapy administration are the main factors that predict survival outcomes of PMCT patients. Interactive nomogram was developed based on significant predictors. Conclusions PMCTs have remained one of the most lethal diseases with poor survival outcome. Survival rate improved during the timeline in AA patients, but in general, racial differences in survival outcome were not observed.

In recent years, an international consortium of research organizations conducted investigations at the Chicxulub Crater in Yucatan, Mexico, to better understand the crater’s formation mechanisms and the effects produced by the impact of the asteroid that is hypothesized to have caused one of the major life extinctions on Earth. This study aims to reproduce the asteroid’s impact mechanics by matching computer simulations obtained with the use of the distinct element method (DEM) against the latest topographic data observed across the crater footprint. A 2D model was formulated using ITASCA’s PFC2D software to reproduce the asteroid’s impact on Earth. The model ground conditions prior to impact were replicated based on available geological and geophysical field information. Also, the proposed DEM model configuration was designed to reproduce a far-field effect to ascertain the energy dissipation of the asteroid’s impact at the model’s boundaries. Impact conditions of the asteroid were defined based on previous asteroid impact investigations. A parametric analysis including the asteroid’s impact angle and the asteroid’s impact velocity was conducted to assess their influence on the crater formation process. Results of the simulations included the final crater topography and stratigraphy, stress profiles, contact force chains, and velocity fields. Numerical simulations showed that both the asteroid velocity and impact inclination play a major role in the crater formation process, and that the use of DEM provides interesting insights into impact crater formation.

BackgroundCyber defense is reactive and slow. On average, the time-to-remedy is hundreds of times larger than the time-to-compromise. In response, Human Digital Twins (HDTs) offer the capability of running massive simulations across multiple domains on the Metaverse. Simulated results may predict adversaries' behaviors and tactics, leading to more proactive cyber defense strategies. However, current HDTs’ cognitive architectures are underdeveloped for such use. ObjectiveThis paper aims to make a case for extending the current digital cognitive architectures as the first step toward more robust HDTs that are suitable for realistic Metaverse cybersecurity simulations. MethodsThis study formally documented 108 psychology constructs and thousands of related paths based on 20 time-tested psychology theories, all of which were packaged as Cybonto—a novel ontology. Then, this study applied 20 network science centrality algorithms in ranking the Cybonto psychology constructs by their influences. ResultsOut of 108 psychology constructs, the top 10 are Behavior, Arousal, Goals, Perception, Self-efficacy, Circumstances, Evaluating, Behavior-Controllability, Knowledge, and Intentional Modality. In this list, only Behaviors, Goals, Perception, Evaluating, and Knowledge are parts of existing digital cognitive architectures. Notably, some of the constructs are not explicitly implemented. Early usability tests demonstrate that Cybonto can also be useful for immediate uses such as manual analysis of hackers’ behaviors and automatic analysis of behavioral cybersecurity knowledge texts. ConclusionsThe results call for specific extensions of current digital cognitive architectures such as explicitly implementing more refined structures of Long-term Memory and Perception, placing a stronger focus on noncognitive yet influential constructs such as Arousal, and creating new capabilities for simulating, reasoning about, and selecting circumstances.

IntroductionPediatric and adult H3K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups.MethodsPubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of H3K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS).ResultsWe included 43 studies comprising 272 adults and 657 pediatric midline gliomas with H3K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of H3.1 K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric H3K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, ACVR1 mutations were more common whereas MGMT methylation, FGFR1, and NF1 mutations were less prevalent in the pediatric cohort.ConclusionPediatric H3K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.

Abstract Background There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients. Methods Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies. Results A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55–0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54–2.26; p-value

IntroductionPineal gland tumors are exceedingly rare and account for 0.4-1.0% of brain neoplasms. Their rarity has confounded a clear understanding of the prognostic factors and standards of care for these neoplasms. In this study, we aimed to investigate the incidence, prognostic indicators, and survival trend of tumors emanating from the pineal gland.MethodsWe accessed the Surveillance, Epidemiology, End Results (SEER) Program for pineal gland tumors from 1975-2016. A multivariate Cox regression model was used to investigate the impact of clinicopathological parameters on all-cause mortality. For survival trend analysis, we employed the Kaplan Meier curve and pairwise comparisons to examine the trend.ResultsWe found 1,792 and 310,003 pineal gland and brain neoplasms during 1975-2016 resulting in an incidence of 0.6%. In the multivariate Cox proportional hazards model, older age, male gender, non-germ cell tumor, and receipt of chemotherapy were significantly associated with poor survival (p < 0.001). The extent of resection and radiotherapy administration did not produce survival advantages. Our result also highlighted an increased survival of pineal gland tumors over the years.ConclusionOur study investigated the prognostic factors that influenced survival in patients with pineal gland tumors. Chemotherapy use adversely affected patient outcomes and should be considered carefully in specific circumstances to avoid its harmful effects. These findings provide important evidence to improve current standards of care for this rare group of tumors. The survival of pineal tumors has improved over time reflecting improvements in current practice.

Objective: Regional burn centers face challenges in follow-up care for large catchment areas. In 2006, we implemented a store-and-forward outpatient protocol (“BurnPics”) for established burn patients in our region to assess healing and range of motion. Starting August 2014, we added videoconferencing visits for select patients. The purpose of this quality improvement project was to evaluate BurnPics and videoconferencing utilization. Methods: We reviewed records of patients enrolled in the BurnPics program from August 2014 through July 2015. We evaluated videoconferencing enrollment, provider time, and revenue generation. Data was analyzed using descriptive statistics. Results: There were 398 BurnPics patients. Most patients resided in-state (82%). Median distance from residence to burn center was 67 miles (IQR 29–228). Fifty-three patients underwent 85 videoconferencing visits; 30 visits (35%) were billable, 27 visits (32%) were post-operative follow-ups, and 28 visits (33%) were not billable due to out-of-state residence. Median time per video-visit was 46 min (IQR 35–60); median burn care provider time was 11 min (IQR 7–14). Conclusions: The BurnPics program has potential to mitigate challenges of follow-up burn care. Videoconferencing has improved our follow-up care and created minimal time burden on providers. Future legislative efforts will help minimize financial and legal barriers to successful regional telehealth programs. Keywords: Telehealth, Burn, Store-and-forward, Videoconferencing

Background In response to increasing mass casualty events nationwide, the American College of Surgeons Committee on Trauma developed a bleeding control course (Stop the Bleed) to teach hemorrhage control techniques to laypeople. There is a high level of public interest in learning about injury mitigation, but no study evaluating learners’ perspectives after bleeding control training. We sought to evaluate the didactic value of the bleeding control course by analyzing learners’ feedback within the framework of adult learning theory.Study design We analyzed a total of 720 open-ended surveys from 20 regional bleeding control courses taught by a level I trauma center team during a 9-month period. Major themes expressed by learners were organized into a categorical code structure. Keywords identified from free text responses were used to code comments into subthemes. These themes were organized into categories within the framework of adult learning theory.Results The two primary themes identified from learners’ feedback were empowerment and practicality. Respondents reported an overwhelmingly positive experience; 97% of participants would recommend the course to others. The course design (lecture, didactics and hands-on activities) was cited as a positive element of the course. Participants felt empowered and prepared to act and help others during mass emergency events. Actionable items for future course improvement were identified.Conclusion Themes from learners’ feedback fit within the framework of adult learning theory. These findings highlight the bleeding control course as an empowering experience and a practical and engaging approach to teaching hemorrhage mitigation to the public.Level of evidence Level V, qualitative analysis.

We demonstrate transmission of a 200-Gb/s superchannel over 3-km single-mode optical fiber (SMF) targeting intra-data center interconnect applications using a novel single-section quantum-well passive-mode-locked laser that generates an optical frequency comb. The transmitted optical signal consists of 16 subcarriers filtered from the optical frequency comb of the laser and modulated with an advanced modulation format of Baudrate-pilot-aided quadrature phase-shift keying (QPSK) modulation that enables direct detection. Bit error rates below the forward error correction limit have been confirmed for all subcarriers, and the detailed noise characteristics of the passive-mode-locked laser have been investigated to support the understanding of the system performance.

Background. Older trauma patients often undergo computed tomography (CT) as part of the initial work-up. CT imaging can also be used opportunistically to measure bone density and assess osteoporosis. Methods. In this retrospective cohort study, osteoporosis was ascertained from admission CT scans in women aged ≥65 admitted to the ICU for traumatic injury during a 3-year period at a single, safety-net, level 1 trauma center. Osteoporosis was defined by established CT-based criteria of average L1 vertebral body Hounsfield units

Burn demographics, prevention and care have changed considerably since the 1970s. The objectives were to 1) identify new and confirm previously described changes, 2) make comparisons to the American Burn Association National Burn Repository, 3) determine when the administration of fluids in excess of the Baxter formula began and to identify potential causes, and 4) model mortality over time, during a 36-year period (1974-2009) at the Harborview Burn Center in Seattle, WA, USA.14,266 consecutive admissions were analyzed in five-year periods and many parameters compared to the National Burn Repository. Fluid resuscitation was compared in five-year periods from 1974 to 2009. Mortality was modeled with the rBaux model. Many changes are highlighted at the end of the manuscript including 1) the large increase in numbers of total and short-stay admissions, 2) the decline in numbers of large burn injuries, 3) that unadjusted case fatality declined to the mid-1980s but has changed little during the past two decades, 4) that race/ethnicity and payer status disparity exists, and 5) that the trajectory to death changed with fewer deaths occurring after seven days post-injury. Administration of fluids in excess of the Baxter formula during resuscitation of uncomplicated injuries was evident at least by the early 1990s and has continued to the present; the cause is likely multifactorial but pre-hospital fluids, prophylactic tracheal intubation and opioids may be involved.1) The dramatic changes include the rise in short-stay admissions; as a result, the model of burn care practiced since the 1970s is still required but is no longer sufficient. 2) Fluid administration in excess of the Baxter formula with uncomplicated injuries began at least two decades ago. 3) Unadjusted case fatality declined to ∼6% in the mid-1980s and changed little since then. The rBaux mortality model is quite accurate.

Sepsis is the primary cause of burn-related mortality and morbidity. Traditional indicators of sepsis exhibit poor performance when used in this unique population due to their underlying hypermetabolic and inflammatory response following burn injury. To address this challenge, we developed the Machine Intelligence Learning Optimizer (MILO), an automated machine learning (ML) platform, to automatically produce ML models for predicting burn sepsis. We conducted a retrospective analysis of 211 adult patients (age ≥ 18 years) with severe burn injury (≥ 20% total body surface area) to generate training and test datasets for ML applications. The MILO approach was compared against an exhaustive "non-automated" ML approach as well as standard statistical methods. For this study, traditional multivariate logistic regression (LR) identified seven predictors of burn sepsis when controlled for age and burn size (OR 2.8, 95% CI 1.99-4.04, P = 0.032). The area under the ROC (ROC-AUC) when using these seven predictors was 0.88. Next, the non-automated ML approach produced an optimal model based on LR using 16 out of the 23 features from the study dataset. Model accuracy was 86% with ROC-AUC of 0.96. In contrast, MILO identified a k-nearest neighbor-based model using only five features to be the best performer with an accuracy of 90% and a ROC-AUC of 0.96. Machine learning augments burn sepsis prediction. MILO identified models more quickly, with less required features, and found to be analytically superior to traditional ML approaches. Future studies are needed to clinically validate the performance of MILO-derived ML models for sepsis prediction.

Tsetse flies (genus Glossina ), the sole vectors of African trypanosomiasis, are distinct from other disease vectors, and most other insects, due to dramatic morphological and physiological adaptations required to support their unique life histories. These evolutionary adaptations are driven by demands associated with their strict dietary and reproductive requirements. Tsetse reproduce by obligate viviparity which entails obligate intrauterine larval development and provisioning of nutrients for the developing larvae. Viviparous reproduction reduces reproductive capacity/rate which also drives increased inter- and intra-sexual competition. Here, we use phase contrast microcomputed tomography (pcMicroCT) to perform a three-dimensional (3D) analysis of viviparity associated morphological adaptations of tsetse female reproductive tract. These include 1) abdominal modifications facilitating the extreme abdominal distention required during blood feeding and pregnancy; 2) abdominal and uterine musculature required for parturition of developed larvae; 3) reduction of ovarian structure and capacity; 4) structural features of the spermatophore form in the female uterus to enhance semen/sperm delivery and inhibition of insemination by competing males; 5) uterine morphological features facilitating expansion and contraction before, during and after pregnancy; 6) milk gland structural optimizations facilitating nutrient incorporation and transfer into the uterus. The use of pcMicroCT provides unprecedented opportunities for examination and discovery of internal morphological features not possible with traditional microscopy techniques and new opportunities for comparative morphological analyses over time and between species.

Recombinant adeno‐associated virus (rAAV) is a commonly used in vivo gene therapy vector because of its nonpathogenicity, long‐term transgene expression, broad tropism, and ability to transduce both dividing and nondividing cells. However, rAAV vector production via transient transfection of mammalian cells typically yields a low fraction of filled‐to‐total capsids (~1%–30% of total capsids produced). Analysis of our previously developed mechanistic model for rAAV2/5 production attributed these low fill fractions to a poorly coordinated timeline between capsid synthesis and viral DNA replication and the repression of later phase capsid formation by Rep proteins. Here, we extend the model by quantifying the expression dynamics of total Rep proteins and their influence on the key steps of rAAV2/5 production using a multiple dosing transfection of human embryonic kidney 293 (HEK293) cells. We report that the availability of preformed empty capsids and viral DNA copies per cell are not limiting to the capsid‐filling reaction. However, optimal expression of Rep proteins (<240 ± 13 ag per cell) enables enrichment of the filled capsid population (>12% of total capsids/cell) upstream. Our analysis suggests increased enrichment of filled capsids via regulating the expression of Rep proteins is possible but at the expense of per cell capsid titer in a triple plasmid transfection. Our study reveals an intrinsic limitation of scaling rAAV2/5 vector genome (vg) production and underscores the need for approaches that allow for regulating the expression of Rep proteins to maximize vg titer per cell upstream. [ABSTRACT FROM AUTHOR]